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• W2594955844 abstract "Proper mammalian fetal gonad development and differentiation is critical for adult reproductive health and fertility, and involves coordinate expression of many genes. Both XX (female) and XY (male) mammalian embryos initially develop bipotential gonads. The Y-linked gene SRY and SOX9 initiate the testicular developmental pathway in XY individuals, whereas recent studies suggest RSPO1 and WNT4 initiate the ovarian developmental pathway in XX individuals. These are two opposing developmental pathways and each involves activation of elaborate genetic networks. However, little is known about the regulation of gene expression and function during this process. Our overall goal is to identify the mechanisms that regulate gene function during fetal ovarian and testicular development. MicroRNAs have been shown to regulate gene expression and function in tissues throughout the body, and likely play a role in mammalian fetal gonad development. MicroRNAs are small non-coding RNAs, ~22 nucleotides in length that are involved in regulating gene expression and function by causing either transcript degradation or translational repression. In this study, we test the hypothesis that microRNAs are expressed during fetal gonad development, and we predict that they play a role in controlling gonadal sex determining gene function. We chose the sheep as an animal model because there are many similarities in fetal gonadal gene expression patterns compared to other mammalian species, including humans. Real time PCR analysis revealed differential expression of conserved microRNAs in fetal sheep gonads at time periods corresponding to sexual differentiation and primordial follicle formation. At gestational day 42, the time period of sexual differentiation in the sheep, 24 of 128 conserved microRNAs were found to be significantly different between testes and ovaries while 43 were differentially expressed at gestational day 75 when primordial follicles begin to form in the fetal ovary. Bioinformatic analysis revealed that several of the differentially expressed microRNAs are predicted to target genes involved in gonad development and differentiation, including SOX9, GATA4, WNT4, FST, and FOXL2. As an example, miR-302d, miR-410 and miR-211 potentially target FOXL2, FST, and WNT4 respectively, and are significantly higher expressed in testes at gestational day 42. These genes are important during fetal ovarian development, and their expression must be tightly regulated in testes for normal testicular development to occur. Results from these studies provide important new insight into the regulation of fetal gonadal development. Improper gene expression or regulation can alter gonadal development leading to abnormalities and infertility. MicroRNAs add another layer of controlling gene function during this crucial process, and can lead to a better understanding of reproductive disorders. (platform)" @default.
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• W2594955844 date "2009-07-01" @default.
• W2594955844 modified "2023-09-27" @default.
• W2594955844 title "Expression of Conserved MicroRNAs in Ovine Fetal Gonads." @default.
• W2594955844 doi "https://doi.org/10.1093/biolreprod/81.s1.36" @default.
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